Aptamers Enhance Oncolytic Viruses’ Antitumor Efficacy

Дымова, М. А.; Kichkailo, Anna S.; Kuligina, Elena V.; Richter, Vladimír

doi:10.3390/pharmaceutics15010151

Cited by 5 publications

(4 citation statements)

References 108 publications

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“…To increase the stability of the aptamer, it is either modified or conjugated with various composite structures (liposomes, dendrimers, nanoparticles, etc.) [ 26 ]. However, when using them in situ, this time is quite sufficient for diagnosing tumor cells [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…To overcome this problem, it may be useful to either evaluate the remaining truncated aptamers for immunoshielding [ 21 ] or perform a SELEX procedure on this particular virus strain, VV-GMCSF-Lact. Additionally, to overcome this issue, one of the possible solutions is to enhance the virus targeting by using a bifunctional aptamer that can bind both to the virus and to neutralizing antibodies [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

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Characterizing Aptamer Interaction with the Oncolytic Virus VV-GMCSF-Lact

Dymova,

Malysheva,

Popova

et al. 2024

Molecules

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Aptamers are currently being investigated for their potential to improve virotherapy. They offer several advantages, including the ability to prevent the aggregation of viral particles, enhance target specificity, and protect against the neutralizing effects of antibodies. The purpose of this study was to comprehensively investigate an aptamer capable of enhancing virotherapy. This involved characterizing the previously selected aptamer for vaccinia virus (VACV), evaluating the aggregation and molecular interaction of the optimized aptamers with the recombinant oncolytic virus VV-GMCSF-Lact, and estimating their immunoshielding properties in the presence of human blood serum. We chose one optimized aptamer, NV14t_56, with the highest affinity to the virus from the pool of several truncated aptamers and built its 3D model. The NV14t_56 remained stable in human blood serum for 1 h and bound to VV-GMCSF-Lact in the micromolar range (Kd≈0.35 μM). Based on dynamic light scattering data, it has been demonstrated that aptamers surround viral particles and inhibit aggregate formation. In the presence of serum, the hydrodynamic diameter (by intensity) of the aptamer–virus complex did not change. Microscale thermophoresis (MST) experiments showed that NV14t_56 binds with virus (EC50 = 1.487 × 109 PFU/mL). The analysis of the amplitudes of MST curves reveals that the components of the serum bind to the aptamer–virus complex without disrupting it. In vitro experiments demonstrated the efficacy of VV-GMCSF-Lact in conjunction with the aptamer when exposed to human blood serum in the absence of neutralizing antibodies (Nabs). Thus, NV14t_56 has the ability to inhibit virus aggregation, allowing VV-GMCSF-Lact to maintain its effectiveness throughout the storage period and subsequent use. When employing aptamers as protective agents for oncolytic viruses, the presence of neutralizing antibodies should be taken into account.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Characterizing Aptamer Interaction with the Oncolytic Virus VV-GMCSF-Lact

Dymova,

Malysheva,

Popova

et al. 2024

Molecules

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“…Oncolytic viruses (OV) are a new class of drugs that have the ability to selectively replicate in tumor cells and lyse targets through a variety of mechanisms, including cytotoxic cytokine directed oncolytic, tumor vascular targeting, and bystander effects [ 67 , 68 ]. OV has a recognized application in cancer immunotherapy [ 69 – 73 ]. As an ideal vector, OV can be payload specific delivered into the tumor environment after administration [ 74 ].…”

Section: The Involvement Of Cd47 In Ovarian Cancer Immunotherapymentioning

confidence: 99%

The biological roles of CD47 in ovarian cancer progression

Xing,

Wang,

Feng

et al. 2024

Cancer Immunol Immunother

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Ovarian cancer is one of the most lethal malignant tumors, characterized by high incidence and poor prognosis. Patients relapse occurred in 65–80% after initial treatment. To date, no effective treatment has been established for these patients. Recently, CD47 has been considered as a promising immunotherapy target. In this paper, we reviewed the biological roles of CD47 in ovarian cancer and summarized the related mechanisms. For most types of cancers, the CD47/Sirpα immune checkpoint has attracted the most attention in immunotherapy. Notably, CD47 monoclonal antibodies and related molecules are promising in the immunotherapy of ovarian cancer, and further research is needed. In the future, new immunotherapy regimens targeting CD47 can be applied to the clinical treatment of ovarian cancer patients.

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“… 15 Nucleic acid aptamers (Apts) are short oligonucleotide fragments, including single-stranded DNA or small molecule RNA, which have shown great potential for targeted diagnosis and treatment of tumors. 16 , 17 Compared with traditional antibodies, Apts have numerous advantages, such as easy screening and synthesis, lower molecular weight, high stability, low immunogenicity, and rapid blood clearance. 18 – 20 A recent study showed that a single-stranded DNA aptamer called S2.2 (5′-GCAGTTGATCCTTTGGATACCCTGG-3′) could specifically bind to MUC1 for BC diagnosis and targeted therapy.…”

Section: Introductionmentioning

confidence: 99%

Use of S2.2/DOX Magnetic Nanoliposomes in MR Molecule Imaging and Targeted Thermochemotherapy for Breast Cancer In Vitro

Zhu

Yang

Guo

et al. 2023

Technol Cancer Res Treat

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Objective To prepare S2.2/DOX magnetic nanoliposomes by combining the potential benefits of MNPs in MRI and the targeted performance of nano-drugs as an innovative method for integrated diagnosis and treatment of breast cancer (BC). Methods We created a S2.2-PEG-MZF/DOX molecular probe by using a lipid material to encapsulate PEG-MZF-NPs and doxorubicin (DOX), and a S2.2 aptamer to target MUC1 to conjugate with PEG-MZF/DOX nanoliposomes. The potential of probe for cell-specific targeting and magnetic resonance (MR) molecular imaging was evaluated by MR scanner and Prussian blue staining. Additionally, we explored the feasibility by using nanoliposome magnetic induction heating to interfere with MCF-7 (MUC1+) BC cells under the influence of an alternating magnetic field (AMF). Results PEG-MZF-NPs were biologically safe. The T2 relaxation rate of PEG-MZF-NPs was found to inhibit T2 signal in a concentration-dependent manner, and the T2 signal of the S2.2-PEG-MZF molecular probe in MCF-7 cells was significantly lower than that in PEG-MZF-NPs group. Moreover, the T2 signal reduction was more pronounced in MCF-7 cells than in the hepatoma cell line HepG2 (MUC1-), suggesting a strong MRI potential of the S2.2-PEG-MZF molecular probe. The S2.2-PEG-MZF/DOX nanoliposome was able to achieve the desired temperature range for tumor hyperthermia (42-44 °C) in vitro. The S2.2-PEG-MZF/DOX nanoliposome accompanied by magnetic fluid hyperthermia (MFH) could inhibit proliferation and invasion and induce apoptosis of MCF-7 cells. The effects of this approach were significantly higher than those observed in the other groups. Conclusion We successfully developed a novel technique for BC diagnosis and treatment using thermochemotherapy under the guidance of MR molecular imaging. This approach holds great potential for improving the management of this devastating disease in the future.

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Aptamers Enhance Oncolytic Viruses’ Antitumor Efficacy

Cited by 5 publications

References 108 publications

Characterizing Aptamer Interaction with the Oncolytic Virus VV-GMCSF-Lact

Characterizing Aptamer Interaction with the Oncolytic Virus VV-GMCSF-Lact

The biological roles of CD47 in ovarian cancer progression

Use of S2.2/DOX Magnetic Nanoliposomes in MR Molecule Imaging and Targeted Thermochemotherapy for Breast Cancer In Vitro

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